Ultrasound-detectable markers, ultrasound system, and methods for monitoring vascular flow and patency

ABSTRACT

An ultrasound-detectable marker, ultrasound system, and methods for monitoring vascular flow and patency are disclosed. The ultrasound-detectable marker comprises one or more resorbable polymers, one or more non-resorbable polymers, one or more non-polymeric materials, or any combinations thereof. The ultrasound-detectable marker is adapted for placement underneath, adjacent to, or above one or more vessels at a postoperative site, such as a vascular anastomosis site. Further, the ultrasound imaging system includes certain user guiding software and/or health analysis software for use with the ultrasound-detectable marker.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application claims the benefit of U.S. Provisional Application No.61/754,177, filed Jan. 18, 2013, and U.S. Provisional Application No.61/819,979, filed May 6, 2013, which are incorporated herein byreference in their entireties.

TECHNICAL FIELD

The presently disclosed subject matter relates generally to noninvasivemethods of monitoring the health of a postoperative site, such as ananastomosis site, and more particularly to an ultrasound-detectablemarker, ultrasound system, and methods for monitoring vascular flow andpatency at postoperative sites.

BACKGROUND

It often is desirable to monitor vascular flow and/or patency at apostoperative site, such as an anastomosis site, following surgery.Noninvasive methods, such as ultrasound imaging, are, in principle,suitable for use in monitoring vascular flow and/or patency ofanastomosis sites. Such monitoring, however, can be challenging because,for example, of (1) the difficulty in locating the postoperative siteand (2) the difficulty in maintaining a linear orientation of thevessels of interest to obtain a useful image.

SUMMARY

In some aspects, the presently disclosed subject matter provides anultrasound-detectable markers for monitoring postoperative site, such asa vascular anastomosis site, wherein the markers comprise one or moreresorbable polymers, one or more non-resorbable polymers, one or morenon-polymeric materials, or any combinations thereof; and wherein themarkers are adapted for placement underneath, adjacent to, or above oneor more vessels at a postoperative site, such as a vascular anastomosissite.

In other aspects, the presently disclosed subject matter provides amethod for monitoring a postoperative site, the method comprising: (a)providing a marker comprising one or more resorbable polymers, one ormore non-resorbable polymers, one or more non-polymeric materials, orany combinations thereof, wherein the marker is adapted for placementunderneath, adjacent to, or above one or more vessels at a postoperativesite; (b) placing the marker underneath, adjacent to, or above at leastone vessel during or after surgery; and (c) using a software algorithmto guide a user with an ultrasound probe to the location of the markerpost-surgery.

In further aspects, the presently disclosed subject matter provides amethod for orienting one or more vessels linearly in a plane duringsurgery, the method comprising: (a) providing a marker comprising one ormore resorbable polymers, one or more non-resorbable polymers, one ormore non-polymeric materials, or any combinations thereof, wherein themarker is adapted for placement underneath, adjacent to, or above one ormore vessels at a postoperative site; (b) placing the marker in asubject during surgery; and (c) placing the one or more vessels on themarker; and wherein the one or more vessels are oriented linearly in aplane after being placed on the marker.

Certain aspects of the presently disclosed subject matter having beenstated hereinabove, which are addressed in whole or in part by thepresently disclosed subject matter, other aspects will become evident asthe description proceeds when taken in connection with the accompanyingDrawings as best described herein below.

BRIEF DESCRIPTION OF THE DRAWINGS

Having thus described the presently disclosed subject matter in generalterms, reference will now be made to the accompanying Drawings, whichare not necessarily drawn to scale, and wherein:

FIG. 1 illustrates a perspective view of an example of the presentlydisclosed ultrasound-detectable marker, wherein theultrasound-detectable marker includes slits;

FIG. 2 illustrates a plan view of the ultrasound-detectable markerincluding slits shown in FIG. 1;

FIG. 3A and FIG. 3B illustrate cross-sectional views of theultrasound-detectable marker shown in FIG. 1;

FIG. 4 illustrates a perspective view of another example of thepresently disclosed ultrasound-detectable marker, wherein theultrasound-detectable marker includes eyelets;

FIG. 5 illustrates a perspective view of the presently disclosedultrasound-detectable marker that further comprises a divider;

FIG. 6, FIG. 7, and FIG. 8 illustrate perspective views of examples ofthe presently disclosed ultrasound-detectable marker when in use;

FIG. 6 illustrates a perspective view of an end-to-end vascularanastomosis site oriented on a presently disclosed ultrasound-detectablemarker;

FIG. 7 illustrates a perspective view of a side-to-side vascularanastomosis site oriented on a presently disclosed ultrasound-detectablemarker;

FIG. 8 illustrates a perspective view of an end-to-side vascularanastomosis site oriented on a presently disclosed ultrasound-detectablemarker;

FIG. 9 illustrates a block diagram of an example of an ultrasoundimaging system that includes certain user guiding software and healthanalysis software for use with the ultrasound-detectable markers;

FIG. 10 is a representation depicting the tendency of postoperativevessels to naturally adopt a tortuous course, which is not amenable tocross-sectional visualization and imaging; and

FIG. 11 is a representation illustrating that the presently disclosedclosed ultrasound-detectable marker can be used to align the vessels topermit visualization;

FIG. 12 illustrates a flow diagram of an example of a method ofmonitoring a vascular anastomosis site during surgery using theultrasound-detectable marker and the ultrasound imaging system;

FIG. 13 illustrates a flow diagram of an example of a method oforienting at least one vessel linearly in a plane during surgery usingthe ultrasound-detectable marker and the ultrasound imaging system;

FIG. 14 illustrates a flow diagram of an example of the process flow ofthe user guiding algorithm of the ultrasound imaging system;

FIG. 15 illustrates a flow diagram of an example of the process flow ofthe health analysis algorithm of the ultrasound imaging system; and

FIG. 16, FIG. 17, FIG. 18, and FIG. 19 illustrate various views of yetother examples of the presently disclosed ultrasound-detectable marker.

DETAILED DESCRIPTION

The presently disclosed subject matter now will be described more fullyhereinafter with reference to the accompanying Drawings, in which some,but not all embodiments of the presently disclosed subject matter areshown. Like numbers refer to like elements throughout. The presentlydisclosed subject matter may be embodied in many different forms andshould not be construed as limited to the embodiments set forth herein;rather, these embodiments are provided so that this disclosure willsatisfy applicable legal requirements. Indeed, many modifications andother embodiments of the presently disclosed subject matter set forthherein will come to mind to one skilled in the art to which thepresently disclosed subject matter pertains having the benefit of theteachings presented in the foregoing descriptions and the associatedDrawings. Therefore, it is to be understood that the presently disclosedsubject matter is not to be limited to the specific embodimentsdisclosed and that modifications and other embodiments are intended tobe included within the scope of the appended claims.

In some embodiments, the presently disclosed subject matter provides anultrasound-detectable marker, ultrasound system, and methods formonitoring vascular flow and patency. In particular embodiments,ultrasound-detectable markers are provided that can be placed at apostoperative site, such as a vascular anastomosis site, and located viaultrasound during or after surgery. The ultrasound-detectable markersprovide a mechanism by which the postoperative site, such as a vascularanastomosis site, may be easily located and then the health of thepostoperative site can be assessed. In other embodiments, an ultrasoundimaging system is provided that includes certain user guiding softwareand/or health analysis software for use with the ultrasound-detectablemarker, whereby the ultrasound imaging system and theultrasound-detectable marker can be used for monitoring vascular flowand patency postoperatively.

As used herein, the term “vasculature” generally means any part of thecirculatory system. More particularly, the term “vasculature” caninclude the arrangement of blood vessels in the body or in an organ orbody part.

As used herein, the term “patency” means the state of being open,unobstructed, or unblocked, for example, a vein or artery that is freeof obstruction.

I. Markers for Monitoring Vascular Flow and Patency Under Ultrasound

Referring now to FIG. 1 and FIG. 2 is a perspective view and a planview, respectively, of an example of the presently disclosedultrasound-detectable marker 100. Further, FIG. 3A shows across-sectional view of the ultrasound-detectable marker 100 taken alongline A-A of FIG. 1 and FIG. 3B shows a cross-sectional view of theultrasound-detectable marker 100 taken along line B-B of FIG. 1.

The ultrasound-detectable marker 100 comprises a body 110 that is, forexample, a plate having a substantially half-pipe or leaf shape (seeFIG. 3B). In one example, the footprint of the ultrasound-detectablemarker 100 is substantially octagonal, as shown in FIG. 1 and FIG. 2.However, the footprint of the ultrasound-detectable marker 100 is notlimited to octagonal. The footprint of the ultrasound-detectable marker100 can be any shape, including, but not limited to, ovular, circular,hexagonal, octagonal, square, rectangular, and the like.

The body 110 of the ultrasound-detectable marker 100 comprises, forexample, one or more resorbable polymers. However, theultrasound-detectable marker 100 is not limited to comprising resorbablepolymers only. The body 110 of the ultrasound-detectable marker 100 caninclude non-polymeric materials, such as metal clips, or a combinationof both resorbable polymers and non-polymeric materials.

As used herein, the term “resorbable” refers to a material, such as apolymeric material, which can be broken down and assimilated into abody. Representative resorbable polymers suitable for use with thepresently disclosed markers include, but are not limited to,poly(lactic-co-glycolic acid) (PLGA), polylactides (PLAs), includingpoly(L-lactide), poly(D-lactide), and poly(DL-lactide), polyglycolide(PGA), polycaprolactone, L-lactide/DL-lactide copolymers,L-lactide/D-lactide copolymers, L-lactide/glycolide copolymers,L-lactide/caprolactone, DL-lactide/glycolide copolymers, andpolyhydroxyalkanoates (PHAs), such as polyhydroxybutyrate (PHB), whichinclude poly-3-hydroxybutyrate (P3HB), poly-4-hydroxybutyrate (P4HB),polyhydroxyvalerate (PHV), polyhydroxyhexanoate (PHH),polyhydroxyoctanoate (PHO), polydioxanone, hyaluronate, chitin,cellulose, collagen, polyethylene glycol, and copolymers thereof.

More particularly, in some embodiments, the presently disclosed markercomprises one or more resorbable polymers selected from the groupconsisting of PLA and PGA. In further embodiments, the one or moreresorbable polymers is PLGA. In still further embodiments, the presentlydisclosed marker comprises two or more resorbable polymer layers,wherein at least two resorbable polymer layers do not comprise the sameresorbable polymer. In other embodiments, the two resorbable polymerlayers comprise PLA and PGA.

In some embodiments, the ultrasound-detectable marker 100 comprises avarying ratio of two or more resorbable polymers. In other embodiments,the ultrasound-detectable marker 100 comprises a varying ratio ofPLA:PGA.

In some embodiments, the ultrasound-detectable marker 100 comprises twoor more resorbable polymer layers and/or a varying ratio of two or moreresorbable polymers, and the presence of two or more resorbable polymerlayers and/or a varying ratio of two or more resorbable polymers createsan impedance change throughout the ultrasound-detectable marker 100.

In still further embodiments of the presently disclosedultrasound-detectable marker 100, microbubbles can be introduced in thepolymer to create impedance changes throughout the volume of theultrasound-detectable marker 100.

By “impedance changes throughout”, it is meant that the majority of theultrasound-detectable marker 100 has variations resulting in animpedance change. For example, more than about 50% to 100% of theultrasound-detectable marker 100 has variations, such as more than 50%,60%, 70%, 80%, 90%, or 99% of the ultrasound-detectable marker 100.Variations in the ultrasound-detectable marker 100 can be made bymanufacturing the ultrasound-detectable marker 100 in layers, by varyingthe ratios of at least two polymers in the ultrasound-detectable marker100, by adding microbubbles to the ultrasound-detectable marker 100, andthe like.

Such variations resulting in impedance changes allow theultrasound-detectable marker 100 to be monitored using an ultrasoundapparatus. Using the presently disclosed methods (see FIG. 12, FIG. 13,FIG. 14, FIG. 15), the site of a previous or ongoing surgery can befound easily and a vessel at the site of surgery can be imaged easily,such as by ultrasound imaging. In addition, the specific site of avascular anastomosis can be determined, monitored, and evaluated for thepresence of patency or blood clotting.

In further embodiments, the ultrasound-detectable marker 100 comprisesone or more non-resorbable polymers. In particular embodiments, the oneor more non-resorbable polymers is selected from the group consisting ofpolycarbonate, polyetheretherketone (PEEK), polypropylene, silicone,polyethylene, and combinations thereof.

Referring again to FIG. 1 and FIG. 2, in some embodiments, theultrasound-detectable marker 100 comprises one or more holes and/orslits 115 adapted to inform a geometric position. The holes or slits 115can be cut through the volume of the ultrasound-detectable marker 100.In the example shown in FIG. 1 and FIG. 2, four slits 115 are providedalong four respective edges of the body 110.

Adding holes and/or slits 115 in an asymmetric fashion to theultrasound-detectable marker 100 aids the presently disclosed softwarealgorithms (see FIG. 9) in determining the orientation of theultrasound-detectable marker 100 in vivo. In other embodiments, eyeletholes can be added to the ultrasound-detectable marker 100 which can beused for attaching, e.g., by suturing, the ultrasound-detectable marker100 to adjacent soft tissue. Accordingly, the ultrasound-detectablemarker 100 comprises at least one eyelet hole adapted to secure theultrasound-detectable marker 100 to soft tissue near the vascularanastomosis site. Namely, FIG. 4 shows another example of theultrasound-detectable marker 100, wherein the ultrasound-detectablemarker 100 includes an eyelet 120 at each end of the body 110, insteadof the holes and/or slits 115. However, in yet other embodiments, theultrasound-detectable marker 100 can include both holes and/or slits 115and eyelets 120.

In some embodiments, the presently disclosed marker comprises a divideradapted to separate at least two blood vessels. Namely, FIG. 5 showsanother example of the ultrasound-detectable marker 100, wherein theultrasound-detectable marker 100 includes a divider 125 protruding froma center portion of the body 110. In further embodiments, the at leasttwo blood vessels are an artery and a vein. In still furtherembodiments, the divider 125 ensures that the blood vessels are inparallel positions.

The ultrasound-detectable marker 100 can be scaled at a variety ofsizes, which accommodate the variety of vessel sizes seen acrossdifferent relevant medical applications. In representative embodiments,and referring again to FIG. 1, FIG. 2, FIG. 3A, and FIG. 3B, theultrasound-detectable marker 100 has a length L, a width W, and athickness T. Further, as shown in FIG. 3B, the substantially half-pipeor leaf shape of the body 110 has a depth D.

The length L of the ultrasound-detectable marker 100 can be, forexample, from about 5 mm to about 80 mm. The width W of theultrasound-detectable marker 100 can be, for example, from about 5 mm toabout 60 mm. The thickness T of the ultrasound-detectable marker 100 canbe, for example, from about 0.5 mm to about 8 mm. The depth D of theultrasound-detectable marker 100 can be, for example, from about 5 mm toabout 25 mm. In one example, the ultrasound-detectable marker 100 has alength L of about 40 mm, a width W of about 25 mm, a thickness T ofabout 2 mm, and a depth D of about 15 mm.

In some embodiments, the ultrasound-detectable marker 100 has adetectable in vivo lifetime during which the ultrasound-detectablemarker 100 remains detectable by ultrasound. In other embodiments, theamount of time that the ultrasound-detectable marker 100 remainsdetectable depends on the type of material that theultrasound-detectable marker 100 is constructed of, the thickness of thematerial, and the like. In further embodiments, theultrasound-detectable marker 100 may remain detectable for days, weeks,months, or many years.

The ultrasound-detectable markers 100 shown in FIG. 1 through FIG. 5 areimplantable resorbable polymeric markers that can be sutured to softtissue via surgical sutures. These markers can be used to locate vesselsof interest and to achieve the proper angle and slice of the vessel.

In certain surgeries, it is desirable to be able to monitor the site ofsurgery during the post-surgery healing period by a noninvasive method,such as ultrasound imaging. The ability to do so is particularlyimportant for vascular surgeries. Examples of vascular surgeries includeanastomoses, which are typically performed on blood vessels, such asarteries and veins.

As used herein, the term “anastomosis” refers to the joining together oftwo hollow structures, for example, two arteries or veins, to restorecontinuity after resection, e.g., a surgical procedure to remove part ofan organ or a tumor or normal tissue around the margin of the tumor, orto bypass unresectable diseased tissue. Such procedures can be performedwith suture material, mechanical staplers, or biodegradable orresorbable glues.

An anastomosis can be end-to-end, side-to-side, or end-to-side dependingon the circumstances of the required reconstruction or bypass procedure.By way of example, FIG. 6, FIG. 7, and FIG. 8 illustrate perspectiveviews of examples of the presently disclosed ultrasound-detectablemarker 100 when in use. Namely, FIG. 6 shows an end-to-end anastomosisin relation to the ultrasound-detectable marker 100, wherein the end ofa first vessel 130 is joined to the end of a second vessel 135 andwherein a joint 140 is formed, for example, using sutures. FIG. 7 showsfirst vessel 130 joined end-to-end with second vessel 135. Further, FIG.7 shows a third vessel 150 is joined to the end of a fourth vessel 155,wherein a joint 160 is formed, for example, using sutures. In thisexample, first vessel 130 and second vessel 135 are separated from andheld parallel to third vessel 150 and fourth vessel 155 via the divider125 of the ultrasound-detectable marker 100. FIG. 8 shows an end-to-sideanastomosis in relation to the ultrasound-detectable marker 100, whereinthe end of the first vessel 130 is joined to the side of the secondvessel 135 and wherein the joint 140 is formed, for example, usingsutures.

Further, the term “reanastomosis” refers to a surgical reconnection, forexample, to reverse a prior surgery to disconnect an anatomicalanastomosis, e.g., tubal reversal after tubal ligation, or to reverse avasectomy. The term “anastomosis” as used herein includes“reanastomosis.”

Most vascular procedures, including, but not limited to, arterial bypassoperations, e.g., a coronary artery bypass, aneurysmectomies, and solidorgan transplants, require vascular anastomoses. In other examples, ananastomosis connecting an artery to a vein also is used to create anarteriovenous fistula, e.g., a cimino fistula, as an access forhemodialysis in patients having end stage renal failure.

Further, resections of gastrointestinal organs, including the esophagus,stomach, small bowel, large bowel, bile ducts, and pancreas, arefollowed by anastomoses to restore continuity. Such resections includebypass operations of the GI tract during bariatric surgery.

In yet further examples, surgical procedures, such as radicalprostatectomy and radical cystectomy, involving the urinary tract,including ureters, urinary bladder, and urethra, can require anastomosisof the bladder to the urethra to restore continuity.

The presently disclosed ultrasound-detectable marker 100 and methods ofuse thereof localize postoperative vessels under ultrasound; providefeedback to the user regarding the location of these vessels; provideimagery of vasculature to determine patency; and provide quantitativeanalysis of vascular flow to monitor vascular health.

Further, the geometry of the presently disclosed ultrasound-detectablemarker 100 provides multi-axis feedback to guide the user to the desiredprobe orientation and view (i.e., both translational and rotationalmovements of the probe).

In some embodiments, the presently disclosed ultrasound-detectablemarker 100 provides an implantable, resorbable marker for monitoringblood vessels after or during post-surgical reconstruction. Theultrasound-detectable marker 100 serves as an indicator, which providesechogenic contrast when viewed under ultrasound, thus allowing medicalpersonnel, e.g., an ultrasound technician, nurse, or doctor, toeffectively and accurately locate the anastomosis site. In addition, thepresently disclosed ultrasound-detectable marker 100 aids in maintaininga linear orientation of the vessel(s) so that the vessel(s) can beimaged. If the vessel is not traveling linearly in a plane, such as ifit is coiled in an “S” shape, for example, the vessel will not be ableto be clearly imaged, such as by ultrasound imaging.

II. System for Monitoring Vascular Flow and Patency Under Ultrasound

In other embodiments, the presently disclosed subject matter includessoftware as described herein below with reference to FIG. 9, whichprovides images and quantitative analysis of the vasculature todetermine patency and volumetric flow rate, thus indicating the overallhealth of the tissue site.

Accordingly, the presently disclosed subject matter provides anultrasound-detectable marker 100 for monitoring a postoperative site,such as a vascular anastomosis site, wherein the ultrasound-detectablemarker 100 comprises one or more resorbable polymers, one or morenon-resorbable polymers, one or more non-polymeric materials, or anycombinations thereof; and wherein the marker is adapted for placementunderneath, adjacent to, or above one or more vessels at thepostoperative site.

FIG. 9 is a block diagram illustrating an ultrasound imaging system 900that includes certain user guiding software and health analysis softwarefor use with the ultrasound-detectable markers 100. It will beunderstood by those having ordinary skill in the art that the ultrasoundimaging system 900, as illustrated in FIG. 9, and the operation thereofas described below, is intended to be generally representative of suchsystems and that any particular system may differ significantly fromthat shown in FIG. 9. The ultrasound imaging system 900 includes atransmit beamformer 910 coupled through a transmit receive (T/R) switch912 to an ultrasound probe 920. While the ultrasound probe 920 may beany transducer probe, in one example, the ultrasound probe 920 is amatrix transducer probe.

In one example, the T/R switch 912 includes one switch element for eachtransducer element. In another example, the ultrasound probe 920includes multiplexing circuitry, or the like, to reduce the number ofrequired switches. The transmit beamformer 910 receives pulsed sequencesfrom a pulse generator 916. The ultrasound probe 920, energized by thetransmit beamformer 910, transmits ultrasound energy into a region ofinterest in a patient's body and receives reflected ultrasound energy,commonly referred to as echoes, from various structures and organswithin the body. As is known by those having ordinary skill in the art,by appropriately delaying the waveforms applied to each transducerelement by the transmit beamformer 910, a focused ultrasound beam may betransmitted from the ultrasound probe 920.

The ultrasound probe 920 is also coupled, through the T/R switch 912, toa receive beamformer 918. Ultrasound energy from a given point withinthe patient's body is received by the transducer elements at differenttimes. The transducer elements convert the received ultrasound energy totransducer signals which may be amplified, individually delayed and thensummed by the receive beamformer 918 to provide a beamformed signal thatrepresents the received ultrasound levels along a desired receive line(“beam”). The receive beamformer 918 may be a digital beamformerincluding an analog-to-digital converter for converting the transducersignals to digital values, or may be an analog beamformer. As known tothose having ordinary skill in the art, the delays applied to thetransducer signals may be varied during reception of ultrasound energyto effect dynamic focusing. The process is repeated for multiple scanlines to create a frame of data for generating an image of the region ofinterest in the patient's body.

The receive beamformed signals are then applied to a signal processor924, which processes the beamformed signal for improved image quality.The receive beamformer 918 and the signal processor 924 comprise anultrasound receiver 926. The output of the signal processor 924 issupplied to a scan converter 928, which converts sector scan and otherscan pattern signals to conventional raster scan display formats. Theoutput of the scan converter 928 is supplied to a display 930, whichdisplays an image of the region of interest in the patient's body.

A system controller 932 provides overall control of the ultrasoundimaging system 900. The system controller 932 performs timing andcontrol functions and typically includes a microprocessor operatingunder the control of graphics generator 936 and control routines 942,both contained within data storage 940. When the desired ultrasoundimage is communicated to the system controller 932, the systemcontroller 932, in cooperation with the control routines 942 and thegraphics generator 936, determines the appropriate scan lines thatshould be projected by the ultrasound probe 920 to achieve the desiredultrasound image communicated to the system controller 932 and displayedat display 930.

The control routines 942 can include standard routines that aretypically found in ultrasound systems, such as, but not limited to,spectral Doppler image processing 944, color Doppler image processing946, and two-dimensional (2D) image processing 948. However, in theultrasound imaging system 900, the control routines 942 further includea user guiding algorithm 950 and a health analysis algorithm 952 for usewith the ultrasound-detectable marker 100.

Namely, the user guiding algorithm 950 is used during surgery when theultrasound-detectable marker 100 is placed in the patient. Further, theuser guiding algorithm 950 is used postoperatively to guide the user tolocate the vascular anastomosis site or the postoperative site (i.e.,locate the ultrasound-detectable marker 100) for monitoring vascularflow and patency. More details of the user guiding algorithm 950 aredescribed herein below with reference to FIG. 14. The health analysisalgorithm 952 is used to measure and display flow data from at least onevessel. More details of the health analysis algorithm 952 are describedherein below with reference to FIG. 15.

Accordingly, using the user guiding algorithm 950 and the healthanalysis algorithm 952, the ultrasound imaging system 900 providesimages and quantitative analysis of the vasculature to determine patencyand volumetric flow rate, thus indicating the overall health of thetissue site.

III. Methods of Monitoring Vascular Flow and Patency Under Ultrasound

The design of the presently disclosed ultrasound-detectable marker 100provides feedback to the user to help orient an ultrasound probeproperly via a specific ultrasound signature. In one embodiment, theultrasound-detectable marker 100 is placed underneath a vessel at thesite of anastomosis in a reconstructive surgical procedure that involvesjoining two vessels, such as shown in FIG. 6, FIG. 7, and FIG. 8.Placement of the ultrasound-detectable marker 100 can be accomplished bysuturing the ultrasound-detectable marker 100 to soft tissue adjacent tothe vessel, by using an adhesive, or by a hooking mechanism. Inembodiments involving suturing, holes and/or slits (e.g., holes and/orslits 115 shown in FIG. 1 and FIG. 2) or small eyelets (e.g., eyelets120 shown in FIG. 4) can be provided in the ultrasound-detectable marker100. In other embodiments, the ultrasound-detectable marker 100 isplaced adjacent to the one or more vessels or above one or more vessels.

The presently disclosed ultrasound-detectable marker 100 can be usedpost-operatively during an ultrasound exam to guide the positioning ofthe probe (e.g., ultrasound probe 920) until the postoperative site,such as an anastomosis site, is found. This navigation process can beperformed using the geometric marker feedback independently, or it canbe performed with the aid of software; namely, the user guidingalgorithm 950 and/or the health analysis algorithm 952. At this point,the medical personnel operating the ultrasound (e.g., ultrasound imagingsystem 900) is able to capture images of the vessels both axially andlongitudinally, in addition to gathering vessel parameters, includingvessel lumen patency and blood flow rate, using the color Dopplerfunction (e.g., color Doppler image processing 946) inherent inultrasound machines known in the art.

In reconstructive surgery applications, such as microvascularreconstruction or “free flap” surgery, this information allows foraccurate examination of vessel function postoperatively to assess theoverall health of the reconstructed tissue and indicate whether clinicalactions should be taken. While many methods of solving the problem ofmonitoring the reconstructed tissue's health have been tried, nonepermit the direct visualization of flow and all suffer from drawbacksthat have prevented any single technology from gaining predominant use(see Smit J M, Zeebregts C J, Acosta R, Werker P M. Advancements in freeflap monitoring in the last decade: a critical review. Plast ReconstrSurg. January 2010; 125(1):177-185). More particularly, the presentlydisclosed ultrasound-detectable marker 100 and methods may allowdetection of clots upon formation well before complete occlusion occurs.Both clinical examination and existing technologies frequently onlydetect complete vessel blockage, by which time it may be too late torestore blood flow and salvage the surgery (see Gimbel M L, Rollins M D,Fukaya E, Hopf H W. Monitoring partial and full venous outflowcompromise in a rabbit skin flap model. Plast Reconstr Surg. September2009; 124(3):796-803). The presently disclosed ultrasound-detectablemarker 100 and methods also can be useful in transplant and vascularsurgeries, as well as in procedures involving urology.

Representative examples illustrating the use of the presently disclosedultrasound-detectable marker 100 are provided in FIGS. 10 and 11.Referring now to FIG. 10, is shown an vascular anastomosis site 1000 inwhich a pair of postoperative vessels 1010 can naturally adopt atortuous course, which is not amenable to cross-sectional visualizationand imaging. In contrast, referring now to FIG. 11, the presentlydisclosed ultrasound-detectable marker 100 aligns the postoperativevessels 1010 to permit visualization, as shown in in vivo swineultrasound images where an artery and vein are easily observed insidethe echogenic marker, e.g., the presently disclosedultrasound-detectable marker 100 (e.g., see inset showing a frame 1020of an ultrasound image).

Accordingly, in some embodiments, the presently disclosed subject matterprovides a method for monitoring a vascular anastomosis site. Inparticular embodiments, the methods are used to monitor a vascularanastomosis site after surgery. For example, FIG. 12 illustrates a flowdiagram of an example of a method 1200 of monitoring a vascularanastomosis site during surgery or post-surgery using theultrasound-detectable marker 100 and the ultrasound imaging system 900.The method 1200 incudes, but it not limited to, the following steps.

At a step 1210, the ultrasound-detectable marker 100 that comprises oneor more resorbable polymers is provided, wherein theultrasound-detectable marker 100 is adapted for placement underneath,adjacent to, or above one or more vessels at a vascular anastomosissite.

At a step 1215, the ultrasound-detectable marker 100 is placedunderneath, adjacent to, or above at least one vessel during or aftersurgery.

At a step 1220, the user guiding algorithm 950 is used postoperativelyto guide a user with an ultrasound probe to the location of theultrasound-detectable marker 100.

In yet other embodiments, the presently disclosed subject matterprovides a method for orienting at least one vessel linearly in a planeduring surgery. For example, FIG. 13 illustrates a flow diagram of anexample of a method 1300 of orienting at least one vessel linearly in aplane during surgery using the ultrasound-detectable marker 100 and theultrasound imaging system 900. The method 1300 includes, but it notlimited to, the following steps.

At a step 1310, the ultrasound-detectable marker 100 that comprises oneor more resorbable polymers is provided, wherein theultrasound-detectable marker 100 is adapted for placement underneath,adjacent to, or above one or more vessels at a vascular anastomosissite.

At a step 1315, the ultrasound-detectable marker 100 is placed in asubject during surgery. Namely, the ultrasound-detectable marker 100 isplaced underneath, adjacent to, or above at least one vessel duringsurgery.

At a step 1320, the one or more vessels are placed on theultrasound-detectable marker 100, wherein the one or more vessels areoriented linearly in a plane after being placed on theultrasound-detectable marker 100.

In other embodiments, the methods further comprise using the userguiding algorithm 950 of the ultrasound imaging system 900 of FIG. 9 toguide the user with respect to locating the ultrasound-detectable marker100 via ultrasound. For example, FIG. 14 illustrates a flow diagram ofan example of the process flow 1400 of the user guiding algorithm 950 ofthe ultrasound imaging system 900. The process flow 1400 includes, butit not limited to, the following steps.

At a step 1410, ultrasound waves are generated via, for example, thepulse generator 916, the transmit beamformer 910, the T/R switch 912,and the ultrasound probe 920.

At a step 1415, the reflected ultrasound waves are received with atransducer; namely, via the ultrasound probe 920 and the ultrasoundreceiver 926.

At a step 1420, using, for example, the signal processor 924 and thesystem controller 932, at least one B-mode image is generated. As usedherein, the term “B-mode” refers to a two-dimensional cross section ofthe tissue being imaged. More particularly, the term “B-mode” refers toa two-dimensional ultrasound presentation of echo-producing interfacesin a single plane.

At a step 1425, using, for example, the signal processor 924 and thesystem controller 932, the at least one B-mode image is segmented. Asused herein, the term “segmented” refers to the process of partitioninga digital image into multiple segments, e.g., sets of pixels. Such imagesegmentation can be used to simplify and/or change the representation ofan image and is typically used to locate objects and boundaries, e.g.,lines, curves, and the like, in images. More particularly, imagesegmentation is the process of assigning a label to every pixel in animage such that pixels having the same label share certain visualcharacteristics. The end result of image segmentation is a set ofsegments that collectively cover the entire image, or a set of contoursextracted from the image.

At a step 1430, using, for example, the system controller 932 and/or theuser guiding algorithm 950, a template is matched to the defined markershape. As used herein, the process of “template matching,” as in when atemplate is matched to the defined marker shape, refers to a techniquein digital image processing for finding small parts of an image thatmatch a template image, for example, as a way to detect edges in animage. If the template image has strong features, a feature-basedapproach can be used. For templates that do not have strong features, orunder circumstances when the bulk of the template image constitutes thematching image, a template-based approach can be used. In instances whenthe template might not provide a direct match, eigenspaces, e.g.,templates that detail the matching object under a number of differentconditions including, but not limited to, varying perspectives,illuminations, color contrasts, or acceptable matching poses, can beused. In some embodiments, the process of template matching uses aconvolution mask, i.e., a template, tailored to a special feature of thesearch image to be detected.

For example, in representative embodiments, such a method can beimplemented by first choosing a part of the search image to use as atemplate, which can be referred to as the search image S(x, y), where(x, y) represent the coordinates of each pixel in the search image. Thetemplate can be represented as T(x_(t), y_(t)), where (x_(t), y_(t))represents the coordinates of each pixel in the template. The center (orthe origin) of template T(x_(t), y_(t)) can then be moved over each (x,y) point in the search image and the sum of products can be calculatedbetween the coefficients in S(x, y) and T(x_(t), y_(t)) over the wholearea spanned by the template. As all possible positions of the templatewith respect to the search image are considered, the position with thehighest score is the best position.

At a step 1435, using, for example, the system controller 932 and/or theuser guiding algorithm 950, a pose is estimated. By “pose,” is meant thecombination of position and orientation of an object. The pose of anobject is generally determined using image data. In some embodiments,the pose is described by means of a rotation and translationtransformation, which brings the object from a reference pose to theobserved pose. The pose estimation is performed to determine how thetransducer and marker are positioned relative to each other. Forexample, the pose estimation may determine that the transducer iscurrently seeing a rotated view of the marker.

At a step 1440, using, for example, the system controller 932 and/or theuser guiding algorithm 950, a desired pose is calculated. The “desiredpose” is the relative positioning of marker and transducer that onewishes to achieve. This position could be either the very center of themarker (i.e., no translation or rotation), or it could simply be thatthe desired pose is the same transducer/marker relation at which earlierflow measurements were taken and it is desirable to take newmeasurements at exactly the same view on the ultrasound.

At a step 1445, using, for example, the system controller 932 and/or theuser guiding algorithm 950, guidance is provided to the user withrespect to repositioning the ultrasound probe 920 based on the desiredpose. Guidance can be provided by either a display of the marker shapeon which the cross-sectional view that the ultrasound is currentlyobserving is labeled or highlighted or by stepwise correctiveinstructions to achieve the desired pose (e.g., rotate the transducer 30degrees clockwise, move one cm forward, and the like).

In still other embodiments of the process flow 1400, more than oneB-mode image is generated and segmented before matching a template tothe defined marker shape. In further embodiments, the process flow 1400can be repeated until the ultrasound probe 920 is positioned so that thedesired pose is observed.

In some embodiments, the methods further comprise using the healthanalysis algorithm 952 of the ultrasound imaging system 900 to measureand display flow data from at least one vessel. For example, FIG. 15illustrates a flow diagram of an example of the process flow 1500 of thehealth analysis algorithm 952 of the ultrasound imaging system 900. Theprocess flow 1500 includes, but it not limited to, the following steps.

At a step 1510, ultrasound waves are generated via, for example, thepulse generator 916, the transmit beamformer 910, the T/R switch 912,and the ultrasound probe 920.

At a step 1515, the reflected ultrasound waves are received with atransducer; namely, via the ultrasound probe 920 and the ultrasoundreceiver 926.

At a step 1520, using, for example, the system controller 932 and/or thehealth analysis algorithm 952, the desired pose may optionally beconfirmed. This step is optional. Pose estimation (as per above) can beperformed again to confirm that the position is as desired prior tobeginning doppler data collection. For example, if the user was guidedto the center of the marker by the guidance algorithm, but then movedthe probe prior to starting collection of the flow data, inaccurate datacould be obtained. Performing one more pose estimation as part of theDoppler flow data collection process allows confirmation of pose, aswell as recording of the location (pose) at which the data werecollected.

At a step 1525, using, for example, the system controller 932 and/or thehealth analysis algorithm 952, at least one B-mode image and at leastone set of Doppler velocities are collected via, for example, spectralDoppler image processing 944 and color Doppler image processing 946.

At a step 1530, using, for example, the system controller 932 and/or thehealth analysis algorithm 952, a power signal is spatially analyzed todefine the X/Y boundaries of the at least one blood vessel.

At a step 1535, using, for example, the system controller 932 and/or thehealth analysis algorithm 952, multiple frames are temporally analyzedto differentiate the at least one vessel from another vessel.

At a step 1540, using, for example, the system controller 932 and/or thehealth analysis algorithm 952, individual Doppler velocities areintegrated over the calculated X/Y boundaries of the at least onevessel.

At a step 1545, using, for example, the system controller 932 and/or thehealth analysis algorithm 952, the multiple frames are averaged.

At a step 1550, the integrated, averaged Doppler velocities arequantitatively displayed to the user via display 930 or otherwiseindicated to the user.

Referring now to FIG. 16, FIG. 17, FIG. 18, and FIG. 19 are variousviews of yet other examples of the presently disclosedultrasound-detectable markers. Namely, FIG. 16 shows various perspectiveviews of an ultrasound-detectable marker 1600. The body of theultrasound-detectable marker 1600 comprises a pair of ridges 1610, whichflank a trough 1615. This arrangement provides a channel in which one ormore vessels may rest. The body of the ultrasound-detectable marker 1600also comprises holes and/or slits 1620. In this example, the overallfootprint of the ultrasound-detectable marker 1600 has a taper from oneend to the other. In other words, one end of the ultrasound-detectablemarker 1600 is narrower than the other end, as shown.

FIG. 17 shows various perspective views of an ultrasound-detectablemarker 1700. The body of the ultrasound-detectable marker 1700 comprisesa pair of ridges 1710, which flank a trough 1715. This arrangementprovides a channel in which one or more vessels may rest. The body ofthe ultrasound-detectable marker 1700 also comprises a hole and/or slit1720. In this example, the overall footprint of theultrasound-detectable marker 1700 has an hourglass-type of shape. Inother words, the middle region of the ultrasound-detectable marker 1700is narrower than the end regions, as shown.

FIG. 18 shows various perspective views of an ultrasound-detectablemarker 1800. The body of the ultrasound-detectable marker 1800 comprisesa pair of plateaus 1810, which flank a trough 1815. This arrangementprovides a channel in which one or more vessels may rest. The body ofthe ultrasound-detectable marker 1800 also comprises holes and/or slits1820. In this example, the ultrasound-detectable marker 1800 has arectangular table-like structure, as shown.

FIG. 19 shows a perspective view of an ultrasound-detectable marker1900. The body of the ultrasound-detectable marker 1900 comprises a pairof plateaus 1910, which flank a trough 1915. This arrangement provides achannel in which one or more vessels may rest. The body of theultrasound-detectable marker 1900 also comprises holes and/or slits1920. In this example, the ultrasound-detectable marker 1900 has arectangular plate-like structure, as shown.

As described with reference to the ultrasound-detectable markers 100shown in FIG. 1 through FIG. 8, the ultrasound-detectable markers 1600,1700, 1800, 1900 comprise one or more resorbable polymers, one or morenon-resorbable polymers, one or more non-polymeric materials, or anycombinations thereof.

In other embodiments, the presently disclosed methods comprisedetermining a patency and/or a vascular health of at least one vessel.In further embodiments, determining a patency and/or a vascular healthof at least one vessel comprises detecting a blood clot before completeocclusion occurs.

The subject treated by the presently disclosed methods in their manyembodiments is desirably a human subject, although it is to beunderstood that the methods described herein are effective with respectto all vertebrate species, which are intended to be included in the term“subject.”

A “subject” can include a human subject for medical purposes, such asfor the treatment of an existing condition or disease or theprophylactic treatment for preventing the onset of a condition ordisease, or an animal subject for medical, veterinary purposes, ordevelopmental purposes. Suitable animal subjects include mammalsincluding, but not limited to, primates, e.g., humans, monkeys, apes,and the like; bovines, e.g., cattle, oxen, and the like; ovines, e.g.,sheep and the like; caprines, e.g., goats and the like; porcines, e.g.,pigs, hogs, and the like; equines, e.g., horses, donkeys, zebras, andthe like; felines, including wild and domestic cats; canines, includingdogs; lagomorphs, including rabbits, hares, and the like; and rodents,including mice, rats, and the like. An animal may be a transgenicanimal. In some embodiments, the subject is a human including, but notlimited to, fetal, neonatal, infant, juvenile, and adult subjects.Further, a “subject” can include a patient afflicted with or suspectedof being afflicted with a condition or disease. Thus, the terms“subject” and “patient” are used interchangeably herein.

Following long-standing patent law convention, the terms “a,” “an,” and“the” refer to “one or more” when used in this application, includingthe claims. Thus, for example, reference to “a subject” includes aplurality of subjects, unless the context clearly is to the contrary(e.g., a plurality of subjects), and so forth.

Throughout this specification and the claims, the terms “comprise,”“comprises,” and “comprising” are used in a non-exclusive sense, exceptwhere the context requires otherwise. Likewise, the term “include” andits grammatical variants are intended to be non-limiting, such thatrecitation of items in a list is not to the exclusion of other likeitems that can be substituted or added to the listed items.

For the purposes of this specification and appended claims, unlessotherwise indicated, all numbers expressing amounts, sizes, dimensions,proportions, shapes, formulations, parameters, percentages, parameters,quantities, characteristics, and other numerical values used in thespecification and claims, are to be understood as being modified in allinstances by the term “about” even though the term “about” may notexpressly appear with the value, amount or range. Accordingly, unlessindicated to the contrary, the numerical parameters set forth in thefollowing specification and attached claims are not and need not beexact, but may be approximate and/or larger or smaller as desired,reflecting tolerances, conversion factors, rounding off, measurementerror and the like, and other factors known to those of skill in the artdepending on the desired properties sought to be obtained by thepresently disclosed subject matter. For example, the term “about,” whenreferring to a value can be meant to encompass variations of, in someembodiments, ±100% in some embodiments ±50%, in some embodiments ±20%,in some embodiments ±10%, in some embodiments ±5%, in some embodiments±1%, in some embodiments ±0.5%, and in some embodiments ±0.1% from thespecified amount, as such variations are appropriate to perform thedisclosed methods or employ the disclosed compositions.

Further, the term “about” when used in connection with one or morenumbers or numerical ranges, should be understood to refer to all suchnumbers, including all numbers in a range and modifies that range byextending the boundaries above and below the numerical values set forth.The recitation of numerical ranges by endpoints includes all numbers,e.g., whole integers, including fractions thereof, subsumed within thatrange (for example, the recitation of 1 to 5 includes 1, 2, 3, 4, and 5,as well as fractions thereof, e.g., 1.5, 2.25, 3.75, 4.1, and the like)and any range within that range.

Although the foregoing subject matter has been described in some detailby way of illustration and example for purposes of clarity ofunderstanding, it will be understood by those skilled in the art thatcertain changes and modifications can be practiced within the scope ofthe appended claims.

1. An ultrasound-detectable marker for monitoring a postoperative site,wherein the ultrasound-detectable marker comprises one or moreresorbable polymers, one or more non-resorbable polymers, one or morenon-polymeric materials, or any combinations thereof; and wherein theultrasound-detectable marker is adapted for placement underneath,adjacent to, or above one or more vessels at the postoperative site. 2.The ultrasound-detectable marker of claim 1, wherein theultrasound-detectable marker comprises one or more resorbable polymersselected from the group consisting of poly(lactic-co-glycolic acid)(PLGA), a polylactide (PLA), polyglycolide (PGA), polycaprolactone, apolyhydroxyalkanoate (PHA), polydioxanone, polyethylene glycol,collagen, hyaluronate, and copolymers thereof.
 3. Theultrasound-detectable marker of claim 2, wherein the one or moreresorbable polymers is selected from the group consisting of PLA andPGA.
 4. The ultrasound-detectable marker of claim 3, wherein the one ormore resorbable polymers is PLGA.
 5. The ultrasound-detectable marker ofclaim 1, wherein the ultrasound-detectable marker comprises two or moreresorbable polymer layers, wherein at least two resorbable polymerlayers do not comprise the same resorbable polymer.
 6. Theultrasound-detectable marker of claim 5, wherein the two resorbablepolymer layers comprise PLA and PGA.
 7. The ultrasound-detectable markerof claim 1, wherein the ultrasound-detectable marker comprises a varyingratio of two or more resorbable polymers.
 8. The ultrasound-detectablemarker of claim 7, wherein the ultrasound-detectable marker comprises avarying ratio of PLA:PGA.
 9. The ultrasound-detectable marker of claim5, wherein the presence of two or more resorbable polymer layers and/ora varying ratio of two or more resorbable polymers creates an impedancechange throughout the marker.
 10. The ultrasound-detectable marker ofclaim 1, wherein the ultrasound-detectable marker comprises one or morenon-resorbable polymers.
 11. The ultrasound-detectable marker of claim10, wherein the one or more non-resorbable polymers is selected from thegroup consisting of polycarbonate, polyetheretherketone, polypropylene,silicone, polyethylene, and combinations thereof.
 12. Theultrasound-detectable marker of claim 1, wherein theultrasound-detectable marker comprises one or more holes and/or slitsadapted to inform a geometric position.
 13. The ultrasound-detectablemarker of claim 1, wherein the ultrasound-detectable marker comprises atleast one eyelet hole adapted to secure the ultrasound-detectable markerto soft tissue near the postoperative site.
 14. Theultrasound-detectable marker of claim 1, wherein theultrasound-detectable marker comprises a divider adapted to separate atleast two blood vessels.
 15. The ultrasound-detectable marker of claim14, wherein the at least two blood vessels are an artery and a vein. 16.The ultrasound-detectable marker of claim 1, wherein theultrasound-detectable marker has a detectable in vivo lifetime duringwhich the ultrasound-detectable marker remains detectable by ultrasound.17. The ultrasound-detectable marker of claim 1, wherein thepostoperative site comprises a vascular anastomosis site.
 18. A methodfor monitoring a postoperative site, the method comprising: (a)providing an ultrasound-detectable marker comprising one or moreresorbable polymers, one or more non-resorbable polymers, one or morenon-polymeric materials, or any combinations thereof; wherein theultrasound-detectable marker is adapted for placement underneath,adjacent to, or above one or more vessels at the postoperative site; (b)placing the ultrasound-detectable marker underneath, adjacent to, orabove one or more vessels during or after surgery; and (c) using asoftware algorithm to guide a user with an ultrasound probe to thelocation of the ultrasound-detectable marker post-surgery.
 19. Themethod of claim 18, wherein using the software algorithm comprises oneor more of: (a) generating ultrasound waves; (b) receiving reflectedultrasound waves with a transducer; (c) generating at least one B-modeimage; (d) segmenting the at least one B-mode image; (e) matching atemplate to the defined marker shape; (f) estimating a pose; (g)calculating a desired pose; and (h) giving a user guidance onrepositioning the probe based on the desired pose.
 20. The method ofclaim 19, wherein the method is repeated until the probe is positionedso that the desired pose is observed.
 21. The method of claim 19,wherein more than one B-mode image is generated and segmented beforematching a template to the defined marker shape.
 22. The method of claim18, further comprising using a second software algorithm to measure anddisplay flow data from the at least one vessel.
 23. The method of claim22, wherein using the second software algorithm comprises one or moreof: (a) generating ultrasound waves; (b) receiving reflected ultrasoundwaves with a transducer; (c) confirming the desired pose; (d) collectingat least one B-mode image and at least one set of Doppler velocities;(e) spatially analyzing a power signal to calculate X/Y boundaries ofthe at least one vessel; (f) temporally analyzing multiple frames todifferentiate the at least one vessel from another vessel; (g)integrating individual Doppler velocities over the calculated X/Yboundaries of the at least one vessel; (h) averaging the multipleframes; and (i) quantitatively displaying the integrated, averagedDoppler velocities.
 24. The method of claim 18, comprising determining apatency and/or a vascular health of the at least one vessel.
 25. Themethod of claim 24, wherein the determining a patency and/or a vascularhealth of the at least one vessel comprises detecting a blood clotbefore complete occlusion occurs.
 26. The method of claim 18, whereinthe ultrasound-detectable marker comprises two or more resorbablepolymer layers and/or a varying ratio of two or more resorbable polymersand wherein the presence of two or more resorbable polymer layers and/ora varying ratio of two or more resorbable polymers creates an impedancechange throughout the ultrasound-detectable marker.
 27. A method fororienting at least one vessel linearly in a plane during surgery, themethod comprising: (a) providing an ultrasound-detectable markercomprising one or more resorbable polymers, one or more non-resorbablepolymers, one or more non-polymeric materials, or any combinationsthereof; wherein the ultrasound-detectable marker is adapted forplacement underneath, adjacent to, or above one or more vessels at apostoperative site; (b) placing the ultrasound-detectable marker in asubject during surgery; and (c) placing the at least one vessel on theultrasound-detectable marker; and wherein the at least one vessel isoriented linearly in a plane after being placed on theultrasound-detectable marker.
 28. The method of claim 27, wherein the atleast one vessel is oriented in a parallel direction after being placedon the ultrasound-detectable marker.
 29. The method of claim 27, furthercomprising attaching the ultrasound-detectable marker to soft tissueadjacent to the postoperative site.
 30. The method of claim 29, whereinattaching the ultrasound-detectable marker to soft tissue occurs by atleast one method selected from the group consisting of suturing, usingan adhesive, and using a hooking mechanism.
 31. The method of claim 27,wherein the ultrasound-detectable marker comprises a divider to isolateeach of the at least two vessels.
 32. The method of claim 27, whereinthe ultrasound-detectable marker comprises two or more resorbablepolymer layers and/or a varying ratio of two or more resorbable polymersand wherein the presence of two or more resorbable polymer layers and/ora varying ratio of two or more resorbable polymers creates an impedancechange throughout the ultrasound-detectable marker.